This project aims to continue development and validation of a novel microfluidics device developed during Phase I that preserves the maximal viability, recovery, and function of cord blood hematopoietic stem cells (HSC). Allogeneic HSC transplantation is the elective treatment for over 50 life threatening diseases including leukemia and lymphoma. However due to matching donor availability, fewer than 30% of the patients actually receive one. Umbilical cord blood has emerged as a readily available source of HSC as it has been collected and stored in cord blood banks worldwide. However, the number of viable HSC in the units stored today is insufficient to effectively treat adult patients. For the 1yr survval rate of adult patients to be significantly increased from the current ~20% to the 50% - 70% success rate achieved in children, it is estimated that the number of viable HSC in a transplanted cord blood unit has to be increased by a factor of ~3. Studies have shown that the current cord blood processing and banking practices lead to as much as ~90% loss in HSC yield and function, particularly during the shipping delay (36 to 48 hrs) and the centrifugal volume reduction step, leaving only 10 - 20% of the original HSC population for treatment. The new device we developed during Phase I enables simple, immediate processing of cord blood at point of care with minimal equipment and training of personnel, thereby minimizing the loss in viability and yield. Phase I prototypes have demonstrated feasibility of using microfluidics to process entire units of cord and significantly better results than the current industry standards-- ~94% of the CD34+ HSC were recovered with no loss of viability or in vitro progenitor activity (n =12). Phase II aims to: 1. Develop optimized working prototype, validate performance and benchmark against leading centrifugation-based systems used in current cord blood banks. 2. Demonstrate device utility at the point of care in a clinical setting. 3. Ensure device gentleness and biological inertness by characterizing cell activation using flow cytometric immune-phenotyping. 4. Demonstrate significant improvement of in vivo engraftment capacity of recovered cells by engraftment into immune-deficient humanized mouse models. Potential impacts of the project include enabling cord blood to become the primary source of HSC for transplantation, delivering significantly better outcomes for adult patients, and making cord blood banking and HSC-based therapies more effective.